Investigating the potential of lipopeptides for aspergillosis therapy

SHANE SMITH1 ,2, Vanessa Duncan2, Carol Munro1, Deborah O’Neil2

Author address: 

1University of Aberdeen, Aberdeen, UK, 2NovaBiotics, Aberdeen, UK

Abstract: 

Development of safe and effective antifungals for the treatment of aspergillosis remains a significant clinical challenge. A number of microbially derived cationic lipopeptides have been identified as potent in vitro antimicrobial agents, but their non-cell selective mode of action, poor plasma stabilities and immunomodulatory effects have limited their potential as drug candidates in vivo. We have derived a wholly synthetic, first-in-class family of lipopeptides that demonstrate significant activity against Aspergillusin vitro and in vivo. Importantly these lipopeptides are not cytotoxic or haemolytic at log orders above therapeutic ranges, are plasma stable compounds, exhibit a rapid fungicidal mode of action killing germlings as well as hyphae. Visualisation of cell leakage by scanning electron microscopy and microfluidics using fluorescent markers confirmed membranes as the target and site of action of the lipopeptides. The novel lipopeptides we have engineered demonstrate early promise as a new generation of much needed antifungal therapies to address difficult to treat Aspergillus and other fungal infections

2013

abstract No: 

SU02Mo1500

Full conference title: 

Microbiology Society Annual Conference
    • MS 2013